tbuckley/cabot-search huggingface dataset:
Deoxycholic acid induces gastric intestinal metaplasia by activating STAT3 signaling and disturbing gastric bile acids metabolism and microbiota
Authors: Duochen Jin, Keting Huang, Miao Xu, Hongjin Hua, Feng Ye, Jin Yan, Guoxin Zhang, Yun Wang
Journal: Gut Microbes (2022)

Intestinal metaplasia (IM) is the inevitable precancerous stage to develop intestinal-type gastric cancer (GC). Deoxycholic acid (DCA) is the main bile acid (BA) component of duodenogastric reflux and has shown an increased concentration during the transition from chronic gastritis to IM associated with continued STAT3 activation. However, the mechanisms underlying how DCA facilitates IM in the gastric epithelium need exploration. We evaluated IM and bile reflux in corpus tissues from 161 subjects undergoing GC screening. Cell survival and proliferation, proinflammatory cytokine expression and TGR5/STAT3/KLF5 axis activity were measured in normal human gastric cells, cancer cells, and organoid lines derived from C57BL/6, FVB/N and insulin-gastrin (INS-GAS) mice treated with DCA. The effects of DCA on IM development were determined in INS-GAS mice with long-term DCA supplementation, after which the gastric bacterial and BA metabolic profiles were measured by 16S rRNA gene sequencing and LC-MS. We revealed a BA-triggered TGR5/STAT3/KLF5 pathway in human gastric IM tissues. In gastric epithelial cells, DCA promoted proliferation and apoptotic resistance, upregulated proinflammatory cytokines and IM markers, and facilitated STAT3 phosphorylation, nuclear accumulation and DNA binding to the KLF5 promoter. DCA triggered STAT3 signaling and the downstream IM marker KLF5 in mouse gastric organoids in vitro and in vivo. In INS-GAS mice, DCA promoted the accumulation of serum total BAs and accelerated the stepwise development of gastric IM and dysplasia. DCA induced gastric environmental alterations involving abnormal BA metabolism and microbial dysbiosis, in which the Gemmobacter and Lactobacillus genera were specifically enriched. Lactobacillus genus enrichment was positively correlated with increased levels of GCA, CA, T-α-MCA, TCA and β-MCA in DCA-administrated INS-GAS mice. DCA promotes nuclear STAT3 phosphorylation, which mediates KLF5 upregulation associated with gastric inflammation and IM development. DCA disturbs the gastric microbiome and BA metabolism homeostasis during IM induction.
An Ectopic Parathyroid Adenoma Mimicking Submandibular Gland on 99mTc-MIBI Parathyroid Scintigraphy
Authors: Meijie Chen, Song Chen, Xuena Li, Yaming Li
Journal: Clinical Nuclear Medicine (2022)

Abstract A 67-year-old woman complained of continuous low back pain for 4 months. She was referred for a 99m Tc-MIBI parathyroid scintigraphy with neck SPECT/CT imaging. The planar images showed no abnormal uptake. However, on the SPECT/CT scan, a soft tissue nodule with high uptake was noted adjacent to the left submandibular gland, mimicking normal submandibular gland uptake. Pathological examination from surgical specimen showed that it was an ectopic parathyroid adenoma.
At the Heart of Treating Kawasaki Disease: The Search for New Approaches to Prevent Coronary Artery Aneurysms
Authors: Yan Du, Pui Y. Lee
Journal: Arthritis & Rheumatology (2022)

Disclosure Form Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Renal effects of empagliflozin in patients hospitalized for acute heart failure: from the <scp>EMPULSE</scp> trial
Authors: Adriaan A. Voors, Kevin Damman, John R. Teerlink, Christiane E. Angermann, Sean P. Collins, Mikhail Kosiborod, Jan Biegus, João Pedro Ferreira, Michael E. Nassif, Mitchell A. Psotka, Jasper Tromp, Martina Brueckmann, Jonathan P. Blatchford, Afshin Salsali, Piotr Ponikowski
Journal: European Journal of Heart Failure (2022)

Abstract Aim The sodium–glucose cotransporter 2 (SGLT2) inhibitor empagliflozin improved clinical outcomes in patients hospitalized for acute heart failure. In patients with chronic heart failure, SGLT2 inhibitors cause an early decline in estimated glomerular filtration rate (eGFR) followed by a slower eGFR decline over time than placebo. However, the effects of SGLT2 inhibitors on renal function during a hospital admission for acute heart failure remain largely unknown. Methods and results Between 1 and 5 days after a hospitalization for acute heart failure, 530 patients with an eGFR &gt;20 ml/min/1.73 m 2 were randomized to 10 mg of empagliflozin or placebo and treated for 90 days. Renal function and electrolytes were measured at baseline, and after 15, 30 and 90 days. We evaluated the effect of empagliflozin on eGFR over time and the impact of baseline eGFR on the primary hierarchical outcome of death, worsening heart failure events and quality of life. Mean baseline eGFR was 52.4 ml/min/1.73 m 2 in the empagliflozin group and 55.7 ml/min/1.73 m 2 in the placebo group. Empagliflozin caused an initial decline in eGFR (−2 ml/min/1.73 m 2 at day 15 compared to placebo). At day 90, eGFR was similar between empagliflozin and placebo. Investigator‐reported acute renal failure occurred in 7.7% of empagliflozin versus 12.1% of placebo patients. The overall clinical benefit (hierarchical composite of all‐cause death, heart failure events and quality of life) of empagliflozin was unaffected by baseline eGFR. Conclusion In patients hospitalized for acute heart failure, empagliflozin caused an early modest decline in renal function which was no longer evident after 90 days. Acute renal events were similar in both groups. The clinical benefit of empagliflozin was consistent regardless of baseline renal function.
An <i>Ex Vivo</i> Organotypic Culture Platform for Functional Interrogation of Human Appendiceal Cancer Reveals a Prominent and Heterogenous Immunological Landscape
Authors: Jonathan Weitz, Tatiana Hurtado de Mendoza, Herve Tiriac, James Lee, Siming Sun, Bharti Garg, Jay Patel, Kevin Li, Joel Baumgartner, Kaitlin J. Kelly, Jula Veerapong, Mojgan Hosseini, Yuan Chen, Andrew M. Lowy
Journal: Clinical Cancer Research (2022)

Abstract Purpose: Epithelial neoplasms of the appendix are difficult to study preclinically given their low incidence, frequent mucinous histology, and absence of a comparable organ in mice for disease modeling. Although surgery is an effective treatment for localized disease, metastatic disease has a poor prognosis as existing therapeutics borrowed from colorectal cancer have limited efficacy. Recent studies reveal that appendiceal cancer has a genomic landscape distinct from colorectal cancer and thus preclinical models to study this disease are a significant unmet need. Experimental Design: We adopted an ex vivo slice model that permits the study of cellular interactions within the tumor microenvironment. Mucinous carcinomatosis peritonei specimens obtained at surgical resection were cutoff using a vibratome to make 150-μm slices cultured in media. Results: Slice cultures were viable and maintained their cellular composition regarding the proportion of epithelial, immune cells, and fibroblasts over 7 days. Within donor specimens, we identified a prominent and diverse immune landscape and calcium imaging confirmed that immune cells were functional for 7 days. Given the diverse immune landscape, we treated slices with TAK981, an inhibitor of SUMOylation with known immunomodulatory functions, in early-phase clinical trials. In 5 of 6 donor samples, TAK981-treated slices cultures had reduced viability, and regulatory T cells (Treg). These data were consistent with TAK981 activity in purified Tregs using an in vitro murine model. Conclusions: This study demonstrates an approach to study appendiceal cancer therapeutics and pathobiology in a preclinical setting. These methods may be broadly applicable to the study of other malignancies.
Plasma CD27, a Surrogate of the Intratumoral CD27–CD70 Interaction, Correlates with Immunotherapy Resistance in Renal Cell Carcinoma
Authors: Nadine Benhamouda, Ikuan Sam, Nicolas Epaillard, Alain Gey, Letuan Phan, Hang Phuong Pham, Nadège Gruel, Antonin Saldmann, Joséphine Pineau, Milena Hasan, Valentin Quiniou, Camille Nevoret, Virginie Verkarre, Valentina Libri, Sebastien Mella, Clémence Granier, Chloe Broudin, Patrice Ravel, Eléonore De Guillebon, Laetitia Mauge, Dominique Helley, Bernd Jabla, Nathalie Chaput, Laurence Albiges, Sandrine Katsahian, Julien Adam, Arnaud Mejean, Olivier Adotevi, Yann A. Vano, Stéphane Oudard, Eric Tartour
Journal: Clinical Cancer Research (2022)

CD70 is a costimulatory molecule known to activate CD27-expressing T cells. CD27-CD70 interaction leads to the release of soluble CD27 (sCD27). Clear-cell renal cell carcinoma (ccRCC) expresses the highest levels of CD70 among all solid tumors; however, the clinical consequences of CD70 expression remain unclear.Tumor tissue from 25 patients with ccRCC was assessed for the expression of CD27 and CD70 in situ using multiplex immunofluorescence. CD27+ T-cell phenotypes in tumors were analyzed by flow cytometry and their gene expression profile were analyzed by single-cell RNA sequencing then confirmed with public data. Baseline sCD27 was measured in 81 patients with renal cell carcinoma (RCC) treated with immunotherapy (35 for training cohort and 46 for validation cohort).In the tumor microenvironment, CD27+ T cells interacted with CD70-expressing tumor cells. Compared with CD27- T cells, CD27+ T cells exhibited an apoptotic and dysfunctional signature. In patients with RCC, the intratumoral CD27-CD70 interaction was significantly correlated with the plasma sCD27 concentration. High sCD27 levels predicted poor overall survival in patients with RCC treated with anti-programmed cell death protein 1 in both the training and validation cohorts but not in patients treated with antiangiogenic therapy.In conclusion, we demonstrated that sCD27, a surrogate marker of T-cell dysfunction, is a predictive biomarker of resistance to immunotherapy in RCC. Given the frequent expression of CD70 and CD27 in solid tumors, our findings may be extended to other tumors.
Protecting Cardiovascular Health From Wildfire Smoke
Authors: Michael B. Hadley, Sarah B. Henderson, Michael Brauer, Rajesh Vedanthan
Journal: Circulation (2022)

Wildfire smoke is a rapidly growing threat to global cardiovascular health. We review the literature linking wildfire smoke exposures to cardiovascular effects. We find substantial evidence that short-term exposures are associated with key cardiovascular outcomes, including mortality, hospitalization, and acute coronary syndrome. Wildfire smoke exposures will continue to increase over the majority of Earth's surface. For example, the United States alone has experienced a 5-fold increase in annual area burned since 1972, with 82 million individuals estimated to be exposed to wildfire smoke by midcentury. The associated rise in excess morbidity and mortality constitutes a growing global public health crisis. Fortunately, the effect of wildfire smoke on cardiovascular health is modifiable at the individual and population levels through specific interventions. Health systems therefore have an opportunity to help safeguard patients from smoke exposures. We provide a roadmap of evidence-based interventions to reduce risk and protect cardiovascular health. Key interventions include preparing health systems for smoke events; identifying and educating vulnerable patients; reducing outdoor activities; creating cleaner air environments; using air filtration devices and personal respirators; and aggressive management of chronic diseases and traditional risk factors. Further research is needed to test the efficacy of interventions on reducing cardiovascular outcomes.
Myocarditis After <i>BNT162b2</i> COVID-19 Third Booster Vaccine in Israel
Authors: Dror Mevorach, Emilia Anis, Noa Cedar, Tal Hasin, Michal Bromberg, Lital Goldberg, Nir Levi, Ofer Perzon, Nur Magadle, Barhoum Barhoum, Elchanan Parnassa, Rita Dichtiar, Yael Hershkovitz, Manfred S. Green, Nachman Ash, Lital Keinan-Boker, Sharon Alroy-Preis
Journal: Circulation (2022)
Thrombotic Thrombocytopenic Purpura
Authors: James N. George
Journal: New England Journal of Medicine (2006)

A 40-year-old obese black woman has had weakness and epigastric pain for several weeks and diarrhea and vomiting for four days. She does not appear acutely ill; the physical examination is normal except for abdominal tenderness. Her hematocrit is 25 percent. The platelet count is 10,000 per cubic millimeter. The peripheral-blood smear shows occasional fragmented and polychromatophilic red cells. The serum creatinine level is 1.1 mg per deciliter (97.2 μmol per liter), bilirubin 2.5 mg per deciliter (42.8 μmol per liter), and lactate dehydrogenase 722 U per liter (normal, <250). How should this case be managed?
Cluster analysis reveals eosinophilia and fibrosis as poor prognostic markers in 128 patients with eosinophilic fasciitis
Authors: Benjamin Chaigne, Ashley Tieu, Nathanaël Beeker, Elina Zuelgaray, Jean-David Bouaziz, Damien Sène, Nicolas Dupin, Luc Mouthon
Journal: Journal of the American Academy of Dermatology (2022)
Two-drug versus three-drug induction chemotherapy in pediatric acute myeloid leukemia: a randomized controlled trial
Authors: Venkatraman Radhakrishnan, Sameer Bakhshi, Smita Kayal, Cherian Thampy, Ankit Batra, Praveen Kumar Shenoy, Hemanth Kumar, Swaminathan Rajaraman, Shilpi Chaudhary, Reema Bisht, Biswajit Dubashi, Trivadi S. Ganesan
Journal: Blood Cancer Journal (2022)

Abstract The benefit of three-drug induction chemotherapy over a two-drug induction has not been evaluated in pediatric acute myeloid leukemia (AML). We, therefore, conducted a randomized controlled trial to ascertain the benefit of a three-drug induction regimen. Patients aged 1–18 years with newly diagnosed AML were randomized to two cycles of induction chemotherapy with daunorubicin and ara-C (DA) or two cycles of ara-C, daunorubicin, and etoposide (ADE). After induction, patients in both arms received consolidation with two cycles of high-dose ara-C. The study’s primary objective was to compare the event-free survival (EFS) between the two arms. The secondary objectives included comparing the composite complete remission (cCR) rates, overall survival (OS), and toxicities. The study randomized 149 patients, 77 in the DA and 72 in the ADE arm. The median age was 8.7 years, and 92 (62%) patients were males. The median follow-up was 50.9 months. The cCR rate in the DA and ADE arm were 82% and 79% ( p = 0.68) after the second induction. There were 13 (17%) induction deaths in the DA arm and 12 (17%) in the ADE arm ( p = 0.97). The 5-year EFS in the DA and ADE arm was 34.4% and 34.5%, respectively ( p = 0.66). The 5-year OS in the DA and ADE arms was 41.4% and 42.09%, respectively ( p = 0.74). There were no significant differences in toxicities between the regimens. There was no statistically significant difference in EFS, OS, CR, or toxicity between ADE and DA regimens in pediatric AML. The trial was registered with the Clinical Trial Registry of India (Reference number: CTRI/2014/11/005202).
The Effectiveness of the Nicotine Patch for Smoking Cessation
Authors: Michael C. Fiore
Journal: JAMA (1994)

<h3>Objective</h3> —To estimate the overall efficacy and optimal use of the nicotine patch for treating tobacco dependence. <h3>Data Sources.</h3> —Nicotine patch efficacy studies published through September 1993, identified through MEDLINE, Psychological Abstracts, and Food and Drug Administration new drug applications. <h3>Study Selection.</h3> —Double-blind, placebo-controlled nicotine patch studies of 4 weeks or longer with random assignment of subjects, biochemical confirmation of abstinence, and subjects not selected on the basis of specific diseases (eg, coronary artery disease). <h3>Data Extraction.</h3> — Pooled abstinence rates and combined odds ratios (ORs) at end of treatment and 6-month follow-up were examined overall and in terms of patch type (16-hour vs 24-hour), patch treatment duration, dosage reduction (weaning), counseling format (individual vs group), and intensity of adjuvant behavioral counseling. <h3>Data Synthesis.</h3> —Across 17 studies (n=5098 patients) meeting inclusion criteria, overall abstinence rates for the active patch were 27% (vs 13% for placebo) at the end of treatment and 22% (vs 9% for placebo) at 6 months. The combined ORs for efficacy of active patch vs placebo patch were 2.6 at the end of treatment and 3.0 at 6 months. The active patch was superior to the placebo patch regardless of patch type (16-hour vs 24-hour), patch treatment duration, weaning, counseling format, or counseling intensity. The 16-hour and 24-hour patches appeared equally efficacious, and extending treatment beyond 8 weeks did not appear to increase efficacy. The pooled abstinence data showed that intensive behavioral counseling had a reliable but modest positive impact on quit rates. <h3>Conclusions.</h3> —The nicotine patch is an effective aid to quitting smoking across different patch-use strategies. Active patch subjects were more than twice as likely to quit smoking as individuals wearing a placebo patch, and this effect was present at both high and low intensities of counseling. The nicotine patch is an effective smoking cessation aid and has the potential to improve public health significantly. (<i>JAMA</i>. 1994;271:1940-1947)
Increasing cases of Naegleria fowleri during the time of COVID 19; an emerging concern of Pakistan
Authors: Shehroze Tabassum, Aroma Naeem, Saima Gill, Nimra Mumtaz, Maleeka Zamurad Khan, Shehram Tabassum, Risha Naeem, Dattatreya Mukherjee
Journal: International Journal of Surgery (2022)
Diverse Approaches to Gene Therapy of Sickle Cell Disease
Authors: Shanna L. White, Kevyn Hart, Donald B. Kohn
Journal: Annual Review of Medicine (2022)

Sickle cell disease (SCD) results from a single base pair change in the sixth codon of the β-globin chain of hemoglobin, which promotes aggregation of deoxyhemoglobin, increasing rigidity of red blood cells and causing vaso-occlusive and hemolytic complications. Allogeneic transplant of hematopoietic stem cells (HSCs) can eliminate SCD manifestations but is limited by absence of well-matched donors and immune complications. Gene therapy with transplantation of autologous HSCs that are gene-modified may provide similar benefits without the immune complications. Much progress has been made, and patients are realizing significant clinical improvements in multiple trials using different approaches with lentiviral vector-mediated gene addition to inhibit hemoglobin aggregation. Gene editing approaches are under development to provide additional therapeutic opportunities. Gene therapy for SCD has advanced from an attractive concept to clinical reality.
Hypoxia-induced exosomal circPDK1 promotes pancreatic cancer glycolysis via c-myc activation by modulating miR-628-3p/BPTF axis and degrading BIN1
Authors: Jiewei Lin, Xinjing Wang, Shuyu Zhai, Minmin Shi, Chenghong Peng, Xiaxing Deng, Da Fu, Jiancheng Wang, Baiyong Shen
Journal: Journal of Hematology & Oncology (2022)

circRNA has been established to play a pivotal role in tumorigenesis development in a variety of cancers; nevertheless, the biological functions and molecular mechanisms of hypoxia-induced exosomal circRNAs in pancreatic cancer remain largely unknown.Differentially expressed circRNAs in exosomes between hypoxic exosomes and normoxic exosomes in PC cells were verified by RNA sequencing. The expression of circPDK1 in PC tumors and PC patients was evaluated by qRT-PCR and ISH, and the biological functions of circPDK1 in PC were verified through a series of in vitro and in vivo experiments. Using Western blotting, Co-IP, RNA pull-down, ChIP, RIP, dual-luciferase assays, and rescue experiments, the underlying mechanism of circPDK1 was verified.CircPDK1 was highly abundant in PC tumor tissues and serum exosomes and was associated with poor survival. Exosomal circPDK1 significantly promoted PC cell proliferation, migration, and glycolysis both in vitro and in vivo. Mechanistically, circPDK1 could be activated by HIF1A at the transcriptional level and sponges miR-628-3p to activate the BPTF/c-myc axis. In addition, circPDK1 serves as a scaffold that enhances the interaction between UBE2O and BIN1, inducing the UBE2O-mediated degradation of BIN1.We found that circPDK1 was activated by HIF1A at the transcriptional level by modulating the miR-628-3p/BPTF axis and degrading BIN1. Exosomal circPDK1 is a promising biomarker for PC diagnosis and prognosis and represents a potential therapeutic target for PC.
An artificial intelligence model to predict survival and chemotherapy benefits for gastric cancer patients after gastrectomy development and validation in international multicenter cohorts
Authors: Xunjun Li, Zhongya Zhai, Wenfu Ding, Li Chen, Yuyun Zhao, Wenjun Xiong, Yunfei Zhang, Dingyi Lin, Zequn Chen, Wei Wang, Yongshun Gao, Shirong Cai, Jiang Yu, Xinhua Zhang, Hao Liu, Guoxin Li, Tao Chen
Journal: International Journal of Surgery (2022)
Volumetric memory network for interactive medical image segmentation
Authors: Tianfei Zhou, Liulei Li, Gustav Bredell, Jianwu Li, Jan Unkelbach, Ender Konukoglu
Journal: Medical Image Analysis (2022)

Despite recent progress of automatic medical image segmentation techniques, fully automatic results usually fail to meet clinically acceptable accuracy, thus typically require further refinement. To this end, we propose a novel Volumetric Memory Network, dubbed as VMN, to enable segmentation of 3D medical images in an interactive manner. Provided by user hints on an arbitrary slice, a 2D interaction network is firstly employed to produce an initial 2D segmentation for the chosen slice. Then, the VMN propagates the initial segmentation mask bidirectionally to all slices of the entire volume. Subsequent refinement based on additional user guidance on other slices can be incorporated in the same manner. To facilitate smooth human-in-the-loop segmentation, a quality assessment module is introduced to suggest the next slice for interaction based on the segmentation quality of each slice produced in the previous round. Our VMN demonstrates two distinctive features: First, the memory-augmented network design offers our model the ability to quickly encode past segmentation information, which will be retrieved later for the segmentation of other slices; Second, the quality assessment module enables the model to directly estimate the quality of each segmentation prediction, which allows for an active learning paradigm where users preferentially label the lowest-quality slice for multi-round refinement. The proposed network leads to a robust interactive segmentation engine, which can generalize well to various types of user annotations (e.g., scribble, bounding box, extreme clicking). Extensive experiments have been conducted on three public medical image segmentation datasets (i.e., MSD, KiTS19, CVC-ClinicDB), and the results clearly confirm the superiority of our approach in comparison with state-of-the-art segmentation models. The code is made publicly available at https://github.com/0liliulei/Mem3D.